CBX3 promotes clear cell renal carcinoma through PI3K/AKT activation and aberrant immunity.
CBX3 promotes clear cell renal carcinoma through PI3K/AKT activation and aberrant immunity.
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DOI：
10.1186/s12967-023-04478-9
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发表时间：
2023-09-06
影响因子：
7.4
通讯作者：
Zhong, Xiaoping
中科院分区：
文献类型：
--
作者：
Chen, Jiasheng;Lin, Yuxin;Zheng, Shukai;Chen, Qingshan;Tang, Shijie;Zhong, Xiaoping
染色体盒同源物 3 (CBX3) 在多种癌症中升高，并显着促进恶性行为；尽管如此，其在透明细胞肾细胞癌（ccRCC）中的确切参与尚不清楚。癌症基因组图谱数据库用于评估 CBX3 的产生及其与 ccRCC 患者生存的关系。我们的团队使用体外和体内模型评估了 ccRCC 细胞群中 CBX3 水平敲低的影响。使用蛋白质印迹和免疫组织化学测定在 ccRCC 细胞中测量 CBX3、与死亡相关的蛋白质以及上皮间质转化 (EMT) 相关蛋白质。通过京都基因和基因组百科全书（KEGG）和基因本体论（GO）以及基因集富集分析（GSEA）的分析，鉴定了与CBX3表达相关的生物学过程和信号通路。使用各种在线工具评估 CBX3 减少的免疫相关活性。基因组和蛋白质表达均表明 ccRCC 中 CBX3 上调。进一步的功能分析表明，CBX3 在体外和体内增强细胞生长、迁移和 EMT 方面发挥着至关重要的作用。此外，研究结果提供了明显的机制证据，表明CBX3通过激活PI3K/AKT通路在ccRCC中发挥其病理功能。最后，免疫分析显示，CBX3（ccRCC 的可能生物标志物）与免疫显着相关。我们的结果表明，CBX3 的过度表达通过 PI3K/AKT 激活甚至免疫失调促进 ccRCC 进展，使其成为潜在可行且有益的治疗靶点。在线版本包含可在 10.1186/s12967-023-04478-9 获取的补充材料。
A chromobox homologue 3 (CBX3) is elevated in various cancers and significantly contributes to the promotion of malignant behavior; despite this, its exact involvement in clear cell renal cell carcinoma (ccRCC) is yet unknown. The Cancer Genome Atlas database served to evaluate CBX3 production and its connection to survival in patients with ccRCC. Our team evaluated the effects of knockdown of CBX3 levels in ccRCC cell populations using in vitro together with in vivo models. CBX3, proteins related to death, and epithelial-to-mesenchymal transition (EMT)-related proteins were measured in ccRCC cells using western blotting and immunohistochemical assays. Through the analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneOntology (GO) and Gene Set Enrichment Analysis (GSEA), the biological processes and signal pathways related to CBX3 expression were identified. Immune-related activity reduced by CBX3 was assessed using various online tools. Both genomic and protein expression showed that CBX3 was upregulated in ccRCC. Further functional analyses revealed that CBX3 played a crucial role in enhancing cell growth, migration, and EMT in vitro along with in vivo. Moreover, the study results provided distinct mechanistic evidence that CBX3 exerts its pathological functions in ccRCC by activating the PI3K/AKT pathway. Finally, immunoassays revealed that CBX3, a possible biomarker of ccRCC, was significantly associated with immunity. Our results suggest that the overexpression of CBX3 promotes ccRCC advancement through PI3K/AKT activation and even immunological dysregulation, making it a potentially viable and beneficial therapeutic target. The online version contains supplementary material available at 10.1186/s12967-023-04478-9.
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影响因子：
7.7
作者：
Keenen MM;Brown D;Brennan LD;Renger R;Khoo H;Carlson CR;Huang B;Grill SW;Narlikar GJ;Redding S
通讯作者：
Redding S
影响因子：
2.5
作者：
Davidsson S;Fiorentino M;Giunchi F;Eriksson M;Erlandsson A;Sundqvist P;Carlsson J
通讯作者：
Carlsson J
影响因子：
5.6
作者：
通讯作者：
--
影响因子：
5.2
作者：
Zhang, Yin Jiang;Zhao, Lin Yi;He, Xu;Yao, Rong Fei;Lu, Fan;Lu, Bi Nan;Pang, Zong Ran
通讯作者：
Pang, Zong Ran
LNCRNA linc00998通过CBX3介导的C-MET/AKT/MTOR轴抑制恶性神经胶质瘤表型。
影响因子：
9
作者：
Cai H;Yu Y;Ni X;Li C;Hu Y;Wang J;Chen F;Xi S;Chen Z
通讯作者：
Chen Z